BACKGROUND: Vitamin D supplementation may prevent falls in older persons, but evidence is inconsistent, possibly because of dosage differences.
OBJECTIVE: To compare the effects of 4 doses of vitamin D3 supplements on falls.
DESIGN: 2-stage Bayesian, response-adaptive, randomized trial. (ClinicalTrials.gov: NCT02166333).
SETTING: 2 community-based research units.
PARTICIPANTS: 688 participants, aged 70 years and older, with elevated fall risk and a serum 25-hydroxyvitamin D [25-(OH)D] level of 25 to 72.5 nmol/L.
INTERVENTION: 200 (control), 1000, 2000, or 4000 IU of vitamin D3 per day. During the dose-finding stage, participants were randomly assigned to 1 of the 4 vitamin D3 doses, and the best noncontrol dose for preventing falls was determined. After dose finding, participants previously assigned to receive noncontrol doses received the best dose, and new enrollees were randomly assigned to receive 200 IU/d or the best dose.
MEASUREMENTS: Time to first fall or death over 2 years (primary outcome).
RESULTS: During the dose-finding stage, the primary outcome rates were higher for the 2000- and 4000-IU/d doses than for the 1000-IU/d dose, which was selected as the best dose (posterior probability of being best, 0.90). In the confirmatory stage, event rates were not significantly different between participants with experience receiving the best dose (events and observation time limited to the period they were receiving 1000 IU/d; n = 308) and those randomly assigned to receive 200 IU/d (n = 339) (hazard ratio [HR], 0.94 [95% CI, 0.76 to 1.15]; P = 0.54). Analysis of falls with adverse outcomes suggested greater risk in the experience-with-best-dose group versus the 200-IU/d group (serious fall: HR, 1.87 [CI, 1.03 to 3.41]; fall with hospitalization: HR, 2.48 [CI, 1.13 to 5.46]).
LIMITATIONS: The control group received 200 IU of vitamin D3 per day, not a placebo. Dose finding ended before the prespecified thresholds for dose suspension and dose selection were reached.
CONCLUSION: In older persons with elevated fall risk and low serum 25-(OH)D levels, vitamin D3 supplementation at doses of 1000 IU/d or higher did not prevent falls compared with 200 IU/d. Several analyses raised safety concerns about vitamin D3 doses of 1000 IU/d or higher.
PRIMARY FUNDING SOURCE: National Institute on Aging.
As a family physician, I find this important in deciding what dose of vitamin D, if any, to advise for patients similar to those in the study.
This confirms previous RCT findings that high-dose Vit D can increase fall risk, and suggests newly that even the 1000 units daily dose may be harmful vis-a-vis injurious falls, even while improving gait speed. Is it possible that the faster gait on the 1000 units daily dose made falls injurious even though fall risk was unchanged?
Over the years there have been different statements about the association between vitamin D and fall risk. There was speculation about the dose that is needed to prevent falls. This study answers the latter question and should put the matter to rest.
The study has no placebo arm, so it merely constitutes a comparison between the effect of two (200 or 1000 units) vitamin D dosages. No difference was found. It would have been informative to have had an untreated control group. An important point could be that too much vitamin D might be harmful.
To me, the most interesting finding of the study is that higher doses of vitamin D3 doses >1000 IU/d may be actually unsafe.
A solid RCT which debunks another Vit D myth, that it reduces falls in the elderly. It is unusual that authors implicitly criticize the National Institute on Aging for insisting on a control group of 200U Vit D instead of placebo, and I agree with them.
Another negative Vitamin D study. This time with safety concerns.